Diabetes-associated alterations in the cecal microbiome and metabolome are independent of diet or environment in the UC Davis Type 2 Diabetes Mellitus Rat model

The composition of the gut microbiome is altered in obesity and type 2 diabetes; however, it is not known whether these alterations are mediated by dietary factors or related to declines in metabolic health. To address this, cecal contents were collected from age-matched, chow-fed male University of California, Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats before the onset of diabetes (prediabetic PD; n = 15), 2 wk recently diabetic (RD; n = 10), 3 mo (D3M; n = 11), and 6 mo (D6M; n = 8) postonset of diabetes. Bacterial species and functional gene counts were assessed by shotgun metagenomic sequencing of bacterial DNA in cecal contents, while metabolites were identified by gas chromatography-quadrupole time-off-flight-mass spectrometry. Metagenomic analysis showed a shift from Firmicutes species in early stages of diabetes (PD + RD) toward an enrichment of Bacteroidetes species in later stages of diabetes (D3M + D6M). In total, 45 bacterial species discriminated early and late stages of diabetes with 25 of these belonging to either Bacteroides or Prevotella genera. Furthermore, 61 bacterial gene clusters discriminated early and later stages of diabetes with elevations of enzymes related to stress response (e.g., glutathione and glutaredoxin) and amino acid, carbohydrate, and bacterial cell wall metabolism. Twenty-five cecal metabolites discriminated early vs. late stages of diabetes, with the largest differences observed in abundances of dehydroabietic acid and phosphate. Alterations in the gut microbiota and cecal metabolome track diabetes progression in UCD-T2DM rats when controlling for diet, age, and housing environment. Results suggest that diabetes-specific host signals impact the ecology and end product metabolites of the gut microbiome when diet is held constant.

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Mechanisms Linking the Gut Microbiome and Glucose Metabolism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-4251 ◽

2016 ◽

Vol 101 (4) ◽

pp. 1445-1454 ◽

Cited By ~ 65

Author(s):

Kristina M. Utzschneider ◽

Mario Kratz ◽

Chris J. Damman ◽

Meredith Hullarg

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glucose Metabolism ◽

Gut Microbiome ◽

Bacterial Species ◽

Hormone Secretion ◽

Bile Acid Metabolism ◽

Gut Hormone

Abstract Context: Type 2 diabetes mellitus is associated with gastrointestinal dysbiosis involving both compositional and functional changes in the gut microbiome. Changes in diet and supplementation with probiotics and prebiotics (ie, fermentable fibers) can induce favorable changes in gut bacterial species and improve glucose homeostasis. Objective: This paper will review the data supporting several potential mechanisms whereby gut dysbiosis contributes to metabolic dysfunction, including microbiota driven increases in systemic lipopolysaccharide concentrations, changes in bile acid metabolism, alterations in short chain fatty acid production, alterations in gut hormone secretion, and changes in circulating branched-chain amino acids. Methods: Data for this review were identified by searching English language references from PubMed and relevant articles. Conclusions: Understanding the mechanisms linking the gut microbiome to glucose metabolism, and the relevant compositional and functional characteristics of the gut microbiome, will help direct future research to develop more targeted approaches or novel compounds aimed at restoring a more healthy gut microbiome as a new approach to prevent and treat type 2 diabetes mellitus and related metabolic conditions.

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The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms22073566 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3566

Author(s):

Chae Bin Lee ◽

Soon Uk Chae ◽

Seong Jun Jo ◽

Ui Min Jerng ◽

Soo Kyung Bae

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glucose Metabolism ◽

Gut Microbiome ◽

Metabolic Disorders ◽

Current Knowledge ◽

Potential Target ◽

The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

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An alcohol-free beer enriched with isomaltulose and a resistant dextrin modulates gut microbiome in subjects with type 2 diabetes mellitus and overweight or obesity: a pilot study

Food & Function ◽

10.1039/d0fo03160g ◽

2021 ◽

Author(s):

Rocío Mateo-Gallego ◽

Isabel Moreno-Indias ◽

Ana M. Bea ◽

Lidia Sánchez-Alcoholado ◽

Antonio J. Fumanal ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Pilot Study ◽

Gut Microbiota ◽

Gut Microbiome ◽

Low Doses ◽

Resistant Dextrin ◽

Overweight Or Obesity

An alcohol-free beer including the substitution of regular carbohydrates for low doses of isomaltulose and maltodextrin within meals significantly impacts gut microbiota in diabetic subjects with overweight or obesity.

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Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2016/3876764 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Sandra Mrozinska ◽

Piotr Radkowski ◽

Tomasz Gosiewski ◽

Magdalena Szopa ◽

Malgorzata Bulanda ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gut Microbiome ◽

Bacterial Flora ◽

Control Group ◽

16S Sequencing ◽

Microbiome Composition ◽

Colonic Flora

Background. Type 2 diabetes mellitus (T2DM) is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY).Methods. The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A-MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed.Results. There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher (p=0.0006) and the amount of Bacteroidetes was lower (p=0.0005) in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group (p=0.0143). At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group.Conclusions. It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.

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The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing A Complex Relationship

Biomedicines ◽

10.3390/biomedicines8010008 ◽

2020 ◽

Vol 8 (1) ◽

pp. 8 ◽

Cited By ~ 13

Author(s):

Angelos K. Sikalidis ◽

Adeline Maykish

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gut Microbiome ◽

Disease Onset ◽

The United States ◽

Key Factors ◽

Fat Diets

Type 2 diabetes mellitus (T2DM) is a disease that affects over 9% of the United States population and is closely linked to obesity. While obesity was once thought to stem from a sedentary lifestyle and diets high in fat, recent evidence supports the idea that there is more complexity pertinent to the issue. The human gut microbiome has recently been the focus in terms of influencing disease onset. Evidence has shown that the microbiome may be more closely related to T2DM than what was originally thought. High fat diets typically result in poor microbiome heath, which then shifts the gut into a state of dysbiosis. Dysbiosis can then lead to metabolic deregulation, including increased insulin resistance and inflammation, two key factors in the development of T2DM. The purpose of this review is to discuss how microbiome relates to T2DM onset, especially considering obesity, insulin resistance, and inflammation.

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Association of adiponectin with dietary factors and cardiovascular risk factors in type 2 diabetes mellitus patients

Diabetes & Metabolic Syndrome Clinical Research & Reviews ◽

10.1016/j.dsx.2013.02.027 ◽

2013 ◽

Vol 7 (1) ◽

pp. 3-7 ◽

Cited By ~ 1

Author(s):

Mohammad Javad Hosseinzadeh Attar ◽

Somayeh Mohammadi ◽

Mehrdad Karimi ◽

Arash Hosseinnezhad ◽

Seyed Hossein Hosseini ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Dietary Factors

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Health potential of polyols as sugar replacers, with emphasis on low glycaemic properties

Nutrition Research Reviews ◽

10.1079/nrr200371 ◽

2003 ◽

Vol 16 (2) ◽

pp. 163-191 ◽

Cited By ~ 191

Author(s):

Geoffrey Livesey

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycaemic Control ◽

Artificial Pancreas ◽

Health Benefits ◽

Dietary Factors ◽

Potential Health ◽

Sugar Replacers

Abstract Polyols are hydrogenated carbohydrates used as sugar replacers. Interest now arises because of their multiple potential health benefits. They are non-cariogenic (sugar-free tooth-friendly), low-glycaemic (potentially helpful in diabetes and cardiovascular disease), low-energy and low-insulinaemic (potentially helpful in obesity), low-digestible (potentially helpful in the colon), osmotic (colon-hydrating, laxative and purifying) carbohydrates. Such potential health benefits are reviewed. A major focus here is the glycaemic index (GI) of polyols as regards the health implications of low-GI foods. The literature on glycaemia and insulinaemia after polyol ingestion was analysed and expressed in the GI and insulinaemic index (II) modes, which yielded the values: erythritol 0, 2; xylitol 13, 11; sorbitol 9, 11; mannitol 0, 0; maltitol 35, 27; isomalt 9, 6; lactitol 6, 4; polyglycitol 39, 23. These values are all much lower than sucrose 65, 43 or glucose 100, 100. GI values on replacing sucrose were independent of both intake (up to 50 g) and the state of carbohydrate metabolism (normal, type 1 with artificial pancreas and type 2 diabetes mellitus). The assignment of foods and polyols to GI bands is considered, these being: high (> 70), intermediate (> 55–70), low (> 40–55), and very low (< 40) including non-glycaemic; the last aims to target particularly low-GI-carbohydrate-based foods. Polyols ranged from low to very low GI. An examination was made of the dietary factors affecting the GI of polyols and foods. Polyol and other food GI values could be used to estimate the GI of food mixtures containing polyols without underestimation. Among foods and polyols a departure of II from GI was observed due to fat elevating II and reducing GI. Fat exerted an additional negative influence on GI, presumed due to reduced rates of gastric emptying. Among the foods examined, the interaction was prominent with snack foods; this potentially damaging insulinaemia could be reduced using polyols. Improved glycated haemoglobin as a marker of glycaemic control was found in a 12-week study of type 2 diabetes mellitus patients consuming polyol, adding to other studies showing improved glucose control on ingestion of low-GI carbohydrate. In general some improvement in long-term glycaemic control was discernible on reducing the glycaemic load via GI by as little as 15–20 g daily. Similar amounts of polyols are normally acceptable. Although polyols are not essential nutrients, they contribute to clinically recognised maintenance of a healthy colonic environment and function. A role for polyols and polyol foods to hydrate the colonic contents and aid laxation is now recognised by physicians. Polyols favour saccharolytic anaerobes and aciduric organisms in the colon, purifying the colon of endotoxic, putrefying and pathological organisms, which has clinical relevance. Polyols also contribute towards short-chain organic acid formation for a healthy colonic epithelium. Polyol tooth-friendliness and reduced energy values are affirmed and add to the potential benefits. In regard to gastrointestinal tolerance, food scientists and nutritionists, physicians, and dentists have in their independent professional capacities each now described sensible approaches to the use and consumption of polyols.

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Gut microbiome differences among Mexican Americans with and without type 2 diabetes mellitus

PLoS ONE ◽

10.1371/journal.pone.0251245 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251245

Author(s):

Amanda K. Kitten ◽

Laurajo Ryan ◽

Grace C. Lee ◽

Bertha E. Flores ◽

Kelly R. Reveles

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Relative Abundance ◽

Gut Microbiome ◽

Beta Diversity ◽

Mexican Americans ◽

Public Health Problem ◽

Shannon Diversity

Purpose Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. Methods This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. Results Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups. Conclusions Although alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.

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